11/10/2016

We are excited to announce SAM Sather’s contribution to the newly released CenterWatch resource "The CRC’s Guide to Coordinating Clinical Research”. SAM has worked within the clinical trial and healthcare industry for around 30 years as a nurse, study coordinator, monitor, auditor, trainer and more. SAM expressed gratitude to CenterWatch for allowing her to update the book.

This book is an invaluable resource for investigative site members and sponsor/CRO stakeholders supporting quality at sites. The book takes a unique approach providing information and regulatory sources, useful checklists and logs, SOP examples, Frequently Asked Questions & Answers, Case Studies, and sample forms to help make this guide even more relevant to your team!

“Your book is a great tool to provide my CRAs as it so clearly states everything that they should know about the CRC's role and the relationship that should be established. Thank you for stating that we are all on the same team looking to achieve the same goal.” - Carolyn Stroud, CEO/President at VIGOR BIOPHARMA SOLUTIONS, Inc.

The following is an excerpt of content that you will find in the book:

(Form pages 16-17)

Electronic Documentation in Clinical Research

Requirements and expectations of paper records will usually also apply to electronic records, but may be implemented differently.

When using paper or electronic documentation, always follow the policies of the organization you are working for. Here are some universally accepted general practices that support many of the good practices for paper though implemented a bit differently.

Attributable:

Authorship should be controlled by assigning roles and responsibilities to ensure only authorized individuals have privileges (e.g., read only vs. edit vs. approve).

Changes made in an electronic database should include requirements for restricted access with assigned roles (e.g., CRCs are provided a specific username and passwords for signing in to an electronic case report form (eCRF) to enter study subject data or answer data queries.)

Legible:

Encrypted documentation can be readable for verification or when printed for research review purposes.

Contemporaneous:

Enter data entries in real time.

There should be a time stamped date and audit trail for both the creation of and changes to documents.

Original:

Original documentation should be available for audit or monitoring. A certified copy should be available as well.

Accurate:

An audit trail should be accessible to confirm the accuracy of the data. The data disclosed should be complete to be able to be verified for accuracy. It is common to have a mix of electronic and paper essential documentation.

(From page 201)

Case Study: Caught in the Middle with Adverse Events

“Help,” the CRC said to the CRA during a monitoring visit for a study looking at a potential new drug for osteoarthritis. “You and my investigator are telling me different things about what adverse events need to be reported. I’m caught in the middle, and I don’t like it.”

The CRC explained that she understood from the investigator’s meeting that all events needed to be reported during the trial, but the investigator told her this was silly and that they certainly wouldn’t do that. He told her that it was too time-consuming to report things that weren’t related to the trial or things they would see in their patients even if they weren’t in the trial (e.g., increased knee pain in a patient with osteoarthritis). “Why would we report colds in an arthritis study?” he told the coordinator. “That just doesn’t make sense, and I’m not going to do it.”

What to do?

First, the CRA told the CRC she would be happy to talk with the investigator and the CRC together about the requirements for adverse event reporting in clinical trials. Here are the points she covered during this discussion:

Clinical trials and clinical practice are not the same. In clinical trials, we know very little about the substances we are putting into people, so we need to collect data on everything that happens to them. There might be a particular event that each involved investigator has seen, and no one thought it was related to the drug, but when the sponsor looked at events over all sites and did an analysis, it was related.

Averse event collection is required by regulation and ICH GCPs.

The protocol is very specific about the procedures for collecting events and specifies that all events occurring during the trial must be collected. When the investigator agreed to do the study, and to follow the protocol, he agreed to do this.

When the investigator signed the 1572 form, he agreed to “report to the sponsor adverse experiences that occur in the course of the investigation in accordance with 21 CFR312.64.” He also agreed to “conduct the study in accordance with the relevant, current protocol.”

Usually, when this kind of situation occurs, the investigator just isn’t fully aware of the relevant responsibilities and will make the necessary changes after these things are pointed out. If this doesn’t happen, what are the next steps to secure compliance?

The next step is for the CRA to alert management. Probably, the sponsor’s medical monitoring, and perhaps a regulatory associate, will call the investigator for further discussion. If the investigator still will not agree to the appropriate reporting of adverse events, the site may have to be closed.

This case study is very common as you can see from our previous blog in which an FDA warning letter was issued to the investigator for failure to comply with the protocol and failing to understand the difference between research and standard care.